Interleukin-5 (IL-5 or IL5) is a lymphokine secreted by T cells and mast cells and biologically activates B cells and eosinophils. The activity on B cells seems to be restricted to the murine system. No detectable activity can be found in a panel of human B-cell activation or differentiation assays. [Clutterbuck et al., Eur. J. Immunol. 17, 1743-1750 (1987)].
In murine hematopoiesis, IL-5 is a selective signal for the proliferation and differentiation of the eosinophilic lineage [Yamaguchi et al., J. Exp. Med. 167, 43-56 (1988)]. In this respect, IL-5 function shows analogies with colony-stimulating factors for other myeloid lineages. Also, human (h) IL-5 is very potent in the activation of human eosinophils [Lopez et al., J. Exp. Med. 167, 219-224 (1988); Saito et al., Proc. Natl. Acad. Sci USA 85, 2288-2292)]. A good discussion of the roles of IL-5 and eosinophils in disease is provided by Sanderson, C. J., Blood, Vol. 79, No. 12 (June 15), 1992, pp. 3101-3109.
Interleukin 5 mediates its activity through a cell membrane receptor-complex. This complex has been characterized physicochemically in both the murine and human system. Mouse pre B cell lines depending on IL5 for their growth have been developed from bone marrow and are used for IL5-receptor analysis [Rolink et al., J. Exp. Med. 169, 1693-1701 (1989)]. The human IL5-receptor (hIL-5R) can be studied on a subclone of the promyelocytic cell line HL60 induced towards eosinophil differentiation [Plaetinck et al., J. Exp. Med. 172, 683-691 (1990)].
Eosinophilic differentiation is initiated using sodium butyrate. Only high affinity (Kd=30 pM) IL5 binding sites can be found on these cells. However cross-linking studies reveal the presence of two polypeptide chains of the receptor involved in IL5 binding, with molecular masses closely resembling the murine IL5R-.alpha.- and -.beta. chains.
Increased half-life in vivo has been shown for example, for chimeric polypeptides consisting of the first two domains or parts thereof of the human CD4-molecule and different domains of the constant regions of the heavy chain or the light chain of a mammalian immunoglobulin (see Traunecker et al., Nature 331, 84-86 [1988] and European Patent Application 90107393.2, Publication No. 394,827).
The specification of European Patent Application 90107393.2, which is the relevant portions of which are described latter in the specification, contains data with respect to the use of pSV-2-derived vectors for the expression of chimeric proteins as well as the construction of vectors for the expression of such chimaeric proteins with other immunoglobulin fragments.
As described above, sources for DNA sequences coding for constant domains of human immunoglobulins are known in the state of the art and disclosed, for example, in EP 394,827 or are described for example by Ellison et al., Nucl. Acid Res. 10, 4071-4079 (1982) for IgG1, or Huck et al., Nucl. Acid Res. 14, 1779-1789 (1986) for IgG3.